This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Learning is perhaps the most malleable form of adaptive behavior and activity-dependent changes in synaptic transmission, such as long-term potentiation (LTP) or long-term depression (LTD), are thought to play a critical role in learning and subsequent memory formation. An emerging issue in the study of activity-dependent synaptic plasticity and its contribution to learning has been the realization that changes initiated at one synapse can spread to other inactive synapses. The induction of LTP at one set of synapses that simultaneously leads to LTD in surrounding inputs to a shared postsynaptic neuron is one example that has been observed in synapses in the hippocampus, visual cortex and amygdala. How this homosynaptic LTP and heterosynaptic LTD are generated, how they interact and their functional relevance is crucial to understanding the cellular basis of learning in particular and adaptive behavior in general. In the leech CNS, induction of LTP in synaptic connections between touch mechanoreceptive neurons (T-cells) and the S-cell (an interneuron known to be critical for some forms of learning of the defensive shortening reflex) also produces LTD in synapses made by non-tetanized T-cells onto the same postsynaptic S-cell. Homosynaptic LTP (homLTP) at T-S synapses is NMDA receptor independent while heterosynaptic LTD is NMDA receptor dependent (Burrell &Sahley, 2004). One possible function of this pattern of plasticity is to "tune" afferent input to a postsynaptic cell leading to improved stimulus specificity. Using the leech model system we propose to examine the cellular mechanisms that mediate homLTP and hetLTD. Furthermore, we will examine how induction of homLTP/hetLTD affects the functional output (in terms of number of action potentials) of the S-cell in response to touch cell input initiated at the skin. Finally, we will determine whether homLTP/hetLTD contributes to stimulus specificity between learned and neutral stimuli during associative learning of the shortening reflex. This project adheres to the Center?s theme of Neural Mechanisms of Adaptive Behavior in that the proposed experiments span from studies of cellular processes mediating neuroplasticity to the effects of such plasticity on learning at the behavioral level.